The retinas of adult fish add new neurons throughout life, and they can regenerate following injury. At least one species of fish, the green sunfish, has a retina that supports a special type of neural regeneration: cone photoreceptors can be anomalously generated and interstitially added into retina that has been mechanically stretched, but is otherwise intact. This proposal presents an experimental program aimed at advancing the understanding of cone photoreceptor production and phenotypic determination during normal retinal growth, retinal regeneration, and interstitial cone addition in stretched retina. The goal of the proposed experiments is to experimentally evaluate the following four specific aims: (1) Study the spatiotemporal formation of cone morphological phenotypes, and the cone mosaic, during retinal regeneration and normal retinal growth. (2) Determine the pattern of opsin expression in the cone mosaic of normal and regenerated retina, as well as in regions of stretched retina where new cones have been interstitially added. (3) Determine if normally proliferative neuroepithelial cells in the retina produce the cones that are interstitially added into stretched retina. (4) Assay for the interstitial addition of inner retinal neurons in stretched retina. The proposed research program emphasizes the production and restoration of cone photoreceptors and other neurons in the adult vertebrate retina. An understanding of these phenomena may ultimately help to generate strategies for the replacement of nerve cells in damaged human retina and brain.